ArticleThe Journal of investigative dermatology2021
Phenformin Promotes Keratinocyte Differentiation via the Calcineurin/NFAT Pathway.
Article in The Journal of investigative dermatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- UV irradiation drives lineage-specific MITF-mediated transcription of PD-L1 to confer immune tolerance to UV-mutated melanocytes.Immunity · 2026Article
- Keratinocyte-specific long non-coding RNA NR037661 controls alternative splicing of ANGPTL4 to induce keratinocyte differentiation.Non-coding RNA research · 2026Article
- Identification of necroptosis & mitophagy-related key genes and their prognostic value in colorectal cancer.Discover oncology · 2025Article
- AMPK in Intestinal Health and Disease: A Multifaceted Therapeutic Target for Metabolic and Inflammatory Disorders.Drug design, development and therapy · 2025Review
- Unveiling the impact of hypodermis on gene expression for advancing bioprinted full-thickness 3D skin models.Communications biology · 2024Article
- Progress in antitumor mechanisms and applications of phenformin (Review).Oncology reports · 2024Review
- Dantrolene corrects cellular disease features of Darier disease and may be a novel treatment.EMBO molecular medicine · 2024Article
- Oral intake of bucillamine, carvedilol, metformin, or phenformin does not protect against UVR-induced squamous cell carcinomas in hairless mice.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2024Article
- Will AMPK be a potential therapeutic target for hepatocellular carcinoma?American journal of cancer research · 2024Review
- Article
- Human skin specific long noncoding RNA HOXC13-AS regulates epidermal differentiation by interfering with Golgi-ER retrograde transport.Cell death and differentiation · 2023Article
- Type 1 and Type 2 Epstein-Barr viruses induce proliferation, and inhibit differentiation, in infected telomerase-immortalized normal oral keratinocytes.PLoS pathogens · 2022Article
- Article
- Epigenetic and metabolic interplay in cutaneous squamous cell carcinoma.Experimental dermatology · 2021Article
- Keratinocyte Carcinoma and Photoprevention: The Protective Actions of Repurposed Pharmaceuticals, Phytochemicals and Vitamins.Cancers · 2021Review
- ATF3 downmodulates its new targets IFI6 and IFI27 to suppress the growth and migration of tongue squamous cell carcinoma cells.PLoS genetics · 2021Article
- Inhibition of Calcineurin/NFAT Signaling Blocks Oncogenic H-Ras Induced Autophagy in Primary Human Keratinocytes.Frontiers in cell and developmental biology · 2021Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Phenformin is a drug in the biguanide class that was previously used to treat type 2 diabetes. We have reported the antitumor activities of phenformin to enhance the efficacy of BRAF-MAPK kinase-extracellular signal-regulated kinase pathway inhibition and to inhibit myeloid-derived suppressor cells in various melanoma models. Here we demonstrate that phenformin suppresses tumor growth and promotes keratinocyte differentiation in the 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate two-stage skin carcinogenesis mouse model. Moreover, phenformin enhances the suspension-induced differentiation of mouse and human keratinocytes. Mechanistically, phenformin induces the nuclear translocation of NFATc1 in keratinocytes in an AMPK-dependent manner. Pharmacologic or genetic inhibition of calcineurin and NFAT signaling reverses the effects of phenformin on keratinocyte differentiation. Taken together, our study reveals an antitumor activity of phenformin to promote keratinocyte differentiation that warrants future translational efforts to repurpose phenformin for the treatment of cutaneous squamous cell carcinomas.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.